One Pill Makes You Small

As recently as three years ago, pharmaceutical companies dared to believe that obesity drugs would become the next mega-blockbusters. Not only would Sanofi-Aventis' rimonabant (branded Acomplia in the EU and Zimulti in the US) begin to turn the tide of a worldwide obesity epidemic, but the new drug—and the other CB1 cannabinoid receptor blockers sure to follow—would also enable these drug giants to survive the expiration of their most valuable patents in 2010 and beyond. The media portrayed the CB1 receptor antagonists as the next wonder drug, promising to quell overeating, arrest the abuse of nicotine and alcohol, and even increase rates of "good" cholesterol.

But by late last year, pharma's hopes for rimonabant had been dashed. As reports of depression and suicide risk accumulated, the drug was mired at FDA, then yanked from the EU market, and finally withdrawn from clinical trials worldwide. In fact, rimonabant was being mentioned in the same breath as Fen-Phen, the diet drug that nearly brought down American Home Products (now Wyeth) in 1997.

Six Obesity Pipeline picks

In November 2008, just one day after Sanofi abandoned its rimonabant obesity program, Pfizer stopped Phase III development on otenabant, its own CB1 receptor antagonist; AstraZeneca, Merck, and Solvay also pulled the plugs on their own versions. In all, 27 obesity drug candidates were shelved during rimonabant's downward spiral in 2007 and 2008, according to Jon Angell, author of Datamonitor's July 2009 report, "Obesity: The $11 Billion Market That Never Was." Angell estimates that pharma's investment in those aborted clinical trials equaled the entire value of the obesity drug market during that time—about $1.1 billion.

In the wake of rimonabant, drugmakers have taken a conservative approach to weight-loss therapies. Instead of radical new mechanisms, the late-stage obesity pipeline now features combinations of already approved drugs and focuses on incremental improvements on drugs that previously failed. None of the half-dozen products likely to seek FDA approval over the next few years promises anything like the $2 billion–plus annual global sales once projected for rimonabant. In fact, the Datamonitor report predicts that most will be lucky to peak at $200 million in worldwide revenue, though other analysts are considerably more optimistic about the drugs' odds for success in this hugely underserved population.